1. Technical Field of the Invention
The present invention relates, generally, to an aqueous composition with an enhanced efficacy in the treatment of acne vulgaris (i.e., common acne) and other skin conditions.
More particularly, the present invention relates to a multifunctional two-part liquid formulation that, upon combination of both phases, either initially ex-vivo or on the skin after sequential application of the two parts, creates a mixture of at least three beneficial acidic substances. These compositions are a complex of various powerful antimicrobial and keratolytic agents, where several of the acid substances serve more than one of these functions.
More specifically, the two-part liquid may be applied sequentially to the subject's skin with either part first applied, or the topical formulation may be applied to the subject's skin after the two parts have been combined. Each of the three alternate methods of application has certain advantages.
2. Description of the Prior Art
The inventive method and composition are directed to the treatment of a number of topical afflictions that heretofore have not been treatable by a multi-functional formulation and often not effectively treatable by any medication or other means. The areas in which this technology can find application includes the broad range of topical skin infections and disinfection, as well as conditions which involve both pathogenic microorganisms and physiologic dysfunction, and often a combination of both. In the latter category is the affliction termed acne, technically acne vulgaris, or common acne.
Acne is a common skin disease that is characterized by areas of skin with seborrhea (scaly red skin), comedones (blackheads and whiteheads), papules (pinheads), pustules (pimples), nodules (large papules) and often scarring. Acne affects mostly skin with the densest population of sebaceous follicles; these areas include the face, the upper part of the chest, and the back. In most cases, acne is an inflammatory condition, but it can also be manifest in non-inflammatory forms. The lesions are caused by hormonal stimulation of the skin's pilosebaceous units, skin structures consisting of hair follicles and their associated sebaceous glands. Increased activity of those gland results in an enhanced secretion of an oily/waxy matter, called sebum, which ordinarily functions to lubricate the skin and hair. Although the primary cause of acne is hyperactivity of the sebaceous gland, it is well recognized that a specific gram-positive microorganism, Propionibacterium acnes, is invariably found in large numbers on the skin of acne sufferers. It lives on the fatty acids in sebum, so the greater the amount of sebum, the greater the quantities of the organism that will be found. It is known that this anaerobic (aerotolerant) bacterium generates enzymes that degrade skin, and also creates proteins that may activate the immune system.
The topical treatment of acne generally involves a material directed to the control of the inflammatory aspect of the condition or the characteristic microorganism (P. acnes) that is present on the skin at levels in excess of normal as a result of the excess sebum “feedstock.” A long-popular component of many topical acne medications is the Rx ingredient benzoyl peroxide. Major factors contributing to its efficacy is its skin-irritating capacity and its capacity to help rid the follicles of excess dead skin cells. This lessens the chance of pore blockage. It has also been theorized to introduce oxygen into the pore, which is anathema to the anaerobic P. acnes. It is not, per se, an antimicrobial agent, as are some of the other topical Rx antibiotics that are employed in the treatment of acne, e.g., clindamycin and erythromycin. The latter, of course, have no keratolytic effect, i.e., the ability to “dissolve” skin cells, breaking the thin skin barriers that cover the comedones, papules, pustules and nodules, and entrap the sebum, which lead to inflamed skin tissue.
The topical retinoid medicines, such as tretinoin, adapalene and tazarotene, are prescription drugs. They have desquamatory effects on the superficial skin layers, promoting drainage of the comedones, papules, etc., which characterize the disease. These topical retinoids may cause mild to moderate irritation in some patients. Although they have no direct antimicrobial activity, these Rx drugs can exert some indirect activity by virtue of the fact that their actions render the follicular microclimate (biofilm) less hospitable to P. acnes. 
The most common material used for the treatment of acne is salicylic acid. This material, a so-called β-hydroxy acid, has recognized keratolytic activity, as do many so-called α-hydroxy acids (“AHAs”; the α-prefix is a measure of the distance of the carbon-bearing hydroxyl group from the terminal carboxylic acid group.) Salicylic acid can “dissolve” skin tissue overlying the papules, pustules, etc., associated with the acne condition. In so doing, it promotes drainage of the blocked sebaceous glands and reduces the resulting inflammatory potential. Associated with the keratolytic activity of salicylic acid is a recognized skin irritancy. The FDA, in its “monograph” on accepted acne materials, allows salicylic acid to be used in acne medications at levels no greater than 2.0%. Obviously, the higher the level, the greater the potential for irritation. Alpha-hydroxy acids are also keratolytic, and to varying degrees have the ability to “dissolve” skin tissue, depending upon the nature of the acid. The most commonly used are glycolic acid and lactic acid. Others found in skin-care products are malic acid, citric acid and tartaric acid and, the recent addition, mandelic acid. Because of concerns over the side effects of certain common α-hydroxy acids, in 1997, the FDA specified that the specific glycolic and lactic AHA concentrations in the product be 10% or less, its pH be 3.5 or higher, and it must have an effective sunscreen in the formulation or warn people to use sunscreen products.
Finally one additional Rx product has been accepted by the FDA for treatment of acne, specifically azelaic acid. It is generally used to treat mild to moderate acne, as both a moderate antibacterial and an anti-inflammatory agent. Interestingly, it doesn't work well for acne that isn't infected with bacteria. Studies show that azelaic acid works as well as other topical Rx formulations (containing such Rx actives as benzoyl peroxide, tretinoin and antibiotics). But it has been reported to take one to two months after starting the application of topical azelaic acid compositions for the acne lesions to start disappearing.
It should be particularly noted that the materials cited above, for the treatment of acne, which are particularly effective, and with the exception of benzoyl peroxide, are all Rx formulations. And even among those that are FDA approved, no component of any of the foregoing formulations is particularly noteworthy for its antimicrobial properties.
Relevant prior art known to the inventor, which addresses the foregoing prior art formulations and treatments, are Yu et al., U.S. Pat. No. 4,105,782, issued Aug. 8, 1978; Warshaw, U.S. Pat. No. 4,450,175, issued May 22, 1984; Song et al., U.S. Pat. No. 5,843,998, issued Dec. 1, 1998; Gross, U.S. Pat. No. 8,017,138 B2, issued Sep. 13, 2011; Bernstein, U.S. Patent Application Publication No. 2005/0084509 A1, issued Apr. 21, 2005; Peters, U.S. Patent Application Publication No. 2008/0311163 A1, issued Dec. 18, 2008; Cunliffe, William J., Acne, Martin Dunitz Ltd., London (1989); and, 21 C.F.R. Part 333, “Topical Acne Drug Products for Over-the-Counter Human Use,” §333.310, disclosing acne active ingredients.
The composition of the present invention is a result of a search for a combination of agents which will provide the high-level antimicrobial activity lacking in the above commercial formulations, while also providing a keratolytic composition that is less irritating than the commercial compositions currently available. And if such a composition could be discovered, it could well have a positive impact on a host of other skin afflictions where microbial proliferation is a major problem. For example there are a number of bacterial skin infections and conditions, such as boils, folliculitis, carbuncles, furuncles, cellulitis, abscesses, impetigo, and erysipelas, where a powerful topical antibacterial composition could be decidedly beneficial. The same can apply to common fungal infections, including athlete's foot, jock itch, ringworm, and yeast infections.